Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53-year-old man underwent chemotherapy (CDDP, VDS, MMC) for treatment of lung cancer. He was given 125 micrograms/m2 of GM-CSF subcutaneously every day for 8 consecutive days, in order to prevent neutropenia. Three days after starting GM-CSF therapy, marked eosinophilia in peripheral blood was observed. The maximum eosinophil count was 89% of leukocytes. Nine days after stopping the treatment with GM-CSF, the number of eosinophils had normalized spontaneously. There were no clinical symptoms except for slight fever, up to 37.5 degrees C. Moreover, there was no relationship between the number of eosinophils and the serum levels of cytokines (IL-3, IL-5, GM-CSF), although we observed minimal but significant elevation of serum ECP level. This case indicates that GM-CSF may induce marked eosinophilia rather than widely stimulating granulocytes and monocytes.
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PMID:[A case of marked eosinophilia in peripheral blood induced by rhGM-CSF]. 812 Oct 93

The present study was designed to investigate the role of neutrophils during the development of Schistosoma japonicum egg granulomas, in C57BL/6 and CBA mice. Laid eggs were implanted into the liver and monoclonal antibody, RB6-8C5, was used to eliminate neutrophils. After daily antibody treatment between days 9 and 13 of egg implantation, both strains of mice showed a marked decrease in neutrophil infiltration and coagulative hepatocyte necrosis at 2 weeks. At 4 weeks, after antibody administration every other day between days 16 and 26, granuloma formation in C57BL/6 mice was not affected by the treatment, whereas CBA mice exhibited a significant increase of reactions. Neutropenia augmented the Th2 cytokine response (IL-4, IL-13 and IL-5), but not for IFN-gamma at any time point examined and in either strain of mice. Higher levels of IL-4 and IL-13 were noted in CBA mice at early and late stages of granuloma formation, compared to C57BL/6 mice. There was also a striking difference in IL-13 production between the two strains. Our results indicate that neutropenia is associated with a significant augmentation of S. japonicum egg-induced granuloma formation in CBA mice, probably through increase in Th2 cytokines, however, the effects differ between early and late stages and between high and low responders.
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PMID:Neutropenia augments experimentally induced Schistosoma japonicum egg granuloma formation in CBA mice, but not in C57BL/6 mice. 1265 90

The mechanisms underlying induction of immune dysregulation and chronic fungal infection by a transient tumor necrosis factor alpha (TNF-alpha) deficiency remain to be defined. The objective of our studies was to determine the potential contribution of neutropenia and immature dendritic cells to the immune deviation. Administration of an anti-TNF-alpha monoclonal antibody at day 0 neutralized TNF-alpha only during the first week of a pulmonary Cryptococcus neoformans infection. Transient neutralization of TNF-alpha resulted in transient depression of interleukin-12 (IL-12), monocyte chemotactic protein 1 (MCP-1), and gamma interferon (IFN-gamma) production but permanently impaired long-term clearance of the infection from the lungs even after the levels of these cytokines increased and a vigorous inflammatory response developed. Early neutrophil recruitment was defective in the absence of TNF-alpha. However, as demonstrated by neutrophil depletion studies, this did not account for the decrease in IL-12 and IFN-gamma levels and did not play a role in establishing chronic pulmonary cryptococcal infection. Transient TNF-alpha neutralization also produced a deficiency in CD11c(+) MHC II(+) cells and IL-12 in the lymph nodes, potentially implicating a defect in mature dendritic cell trafficking. Transfer of cryptococcal antigen-pulsed immature dendritic cells into naive mice prior to intratracheal challenge resulted in the development of a nonprotective immune response to C. neoformans that was similar to that observed in anti-TNF-alpha-treated mice (increased IL-4, IL-5, and IL-10 levels, pulmonary eosinophilia, and decreased clearance). Thus, stimulation of an antifungal response by immature dendritic cells can result in an immune deviation similar to that produced by transient TNF-alpha deficiency, identifying a new mechanism by which a chronic fungal infection can occur in an immunocompetent host.
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PMID:Transient neutralization of tumor necrosis factor alpha can produce a chronic fungal infection in an immunocompetent host: potential role of immature dendritic cells. 1561 39

In acute myeloid leukaemia (AML), age has a definite effect on the biology of the disease and also determines the outcome of chemotherapy. AML cells constitutively express mRNA and produce several haematopoietic cytokines. The haematopoietic cytokines: SCF, IL-3, GM-CSF and G-CSF induce leukaemic colonies or activate DNA synthesis in about 80% of AML cases. Both M-CSF and thrombopoietin stimulated AML cell proliferation is seen in vitro in about 50% of cases. Both IL-6 and IL-11 showed little proliferative activity on primary AML cells. The combinations of these cytokines were synergistic in stimulating the proliferation of AML cells. On the other hand, the inhibitory haematopoietic cytokines: TNF-alpha, TGF-beta, IFN-gamma and IL-4 have shown multiple effects on AML blast cell proliferation. In several in vitro systems, haematopoietic cytokines have failed to induce maturation of AML blasts. Only in AML with t(8;21), G-CSF has induced granulocytic maturation of AML blasts in vitro. AML cells with chromosomal abnormalities involving the 21q22 region differentiate in vitro into eosinophils in the presence of IL-5. IL-6 and IFN-alpha have induced megakaryocytic differentiation of blast cells from acute megakaryoblastic leukemia (M7) patients. The haematopoietic cytokines: SCF, IL-3 and GMCSF have protected in vitro AML cells from chemotherapy-induced apoptosis. Many clinical studies have been recently reported evaluating the effect of the haematopoietic cytokines: GM-CSF, G-CSF, IL-3 and PIXY321 as adjuncts to the chemotherapy of AML patients. Most studies have shown these haematopoietic cytokines to be well-tolerated and effective in augmenting neutrophil recovery in elderly AML patients when given after chemotherapy. On the other hand, considerable number of studies using these cytokines before and during chemotherapy to recruit AML cells into cell cycle and thus make them more susceptible to chemotherapy have reaveled no benefit. Several clinical trials have shown promising results after the use of IL-2 either as remission induction therapy in refractory and/or relapsed AML patients or as post-remission consolidative immunotherapy. Haematopoietic cytokines administered after chemotherapy can shorten the duration of neutropenia and hospitalisation without a significant effect on treatment outcome. On the other hand, their use before and during chemotherapy has yielded no benefit, and instead have led to delay of platelet recovery and worse survival rate in some elderly AML patients.
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PMID:Haematopoietic cytokines in the biology and treatment of acute myeloid leukaemia. 2159 Feb 10

A variety of clinical and laboratory parameters have been used to predict bacteremia. We hypothesize that the generation of a cytokine profile could be used to identify patients at higher risk of bacteremia at the time of presentation with febrile neutropenia. We prospectively evaluated children with cancer who presented with an episode of febrile neutropenia. A multiplexed flow cytometric assay was performed which measured 15 cytokines and chemokines obtained before the initiation of antibiotics. Fifty-eight episodes of chemotherapy-induced febrile neutropenia were included in this study during which 4 patients (7%) had bacteremia. An interleukin-5 level of >8 pg/dL had a sensitivity of 67% and a specificity of 96% to predict bacteremia. An monocyte chemotactic protein-1 level >1650 pg/dL had a sensitivity of 80% and a specificity of 82% to predict bacteremia. Erythrocyte sedimentation rate, C-reactive protein, protein C, and other cytokines/chemokines were not predictive of bacteremia. Elevations of interleukin-5 and monocyte chemotactic protein-1 are predictive of bacteremia in children with cancer who have febrile neutropenia. Prospective studies should be undertaken to determine whether these parameters retain predictive value in a larger series of patients and can select children for outpatient management or early discharge.
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PMID:Predictive value of interleukin-5 and monocyte chemotactic protein-1 for bacteremia in children with febrile neutropenia. 2258 76

Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein, the second CSF, sharing some common effects with granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-5 (IL-5). G-CSF is mainly produced by fibroblasts and endothelial cells from bone marrow stroma and by immunocompetent cells (monocytes, macrophages). The receptor for G-CSF (G-CSFR) is part of the cytokine and hematopoietin receptor superfamily and G-CSFR mutations cause severe congenital neutropenia. The main action of G-CSF - G-CSFR linkage is stimulation of the production, mobilization, survival and chemotaxis of neutrophils, but there are many other G-CSF effects: growth and migration of endothelial cells, decrease of norepinephrine reuptake, increase in osteoclastic activity and decrease in osteoblast activity. In oncology, G-CSF is utilized especially for the primary prophylaxis of chemotherapy-induced neutropenia, but it can be used for hematopoietic stem cell transplantation, it can produce monocytic differentiation of some myeloid leukemias and it can increase some drug resistance. The therapeutic indications of G-CSF are becoming more and more numerous: non neutropenic patients infections, reproductive medicine, neurological disturbances, regeneration therapy after acute myocardial infarction and of skeletal muscle, and hepatitis C therapy.
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PMID:The importance of the granulocyte-colony stimulating factor in oncology. 2673 55